Tubular cells, sodium transport

Reabsorption of Na+ ions is an active process 80% of the total energy expended by the kidneys is used for sodium transport out of the tubular epithelial cell. 

Figure 12.6 Mechanism of action of mineralocortjcoid receptor antagonists in the collecting tubule. Aldosterone enters the tubular cell by the basolateral surface and binds to a specific mineralocorticoid receptor (MNR) in the cytoplasm. The hormone receptor complex triggers the production of an aldosterone-induced protein (AlP) by the cell nucleus (NUC). The AIP acts on the sodium ion channel (ic) to augment the transport of Na+across the basolateral membrane and in to the cell. An increase in AIP activity leads to the recruitment of dormant sodium ion channels and Na pumps (P) in the cell membrane. AIP also leads to the synthesis of new channels and pumps within the cell. The increase in Na+conductance causes electrical changes in the luminal membrane that favour the excretion of intracellular cations, such as K+and H-h. Spironolactone competes with aldosterone for the binding site on the MNR and forms a complex which does not excite the production of AIP by the nucleus.

Ion transport pathways across the luminal and basolateral membranes of the distal convoluted tubule cell. As in all tubular cells, Na+/K+ ATPase is present in the basolateral membrane. NCC is the primary sodium and chloride transporter in the luminal membrane. (R, parathyroid hormone [PTH] receptor.)... 

Q6 Thiazide diuretics are moderately powerful diuretic agents acting on the distal tubule of the nephron. They reduce reabsorption of sodium chloride and water by blocking the electroneutral sodium chloride (NaCl) transporter system at the luminal border of the distal tubular cells. In addition there are direct relaxant effects on vascular smooth muscle which reduces BP. Diuretics help patients in heart failure by reducing peripheral oedema and decreasing blood volume, which in turn reduces BP. In this way both preload and afterload are decreased and the work of the heart is diminished. 

Cell death due to apoptosis or necrosis is not the only form of tubular injury in AKI. There is also sub-lethal injury causing cell dysfunction. For example, alterations in proximal tubular cell polarity occur during renal ischemia. Tubule polarity is essential for its primary function of selective reabsorption of ions from the tubular fluid. Sodium-potassium-ATPase (NaK-ATPase), the enzyme, normally localized to the basolateral membrane, maintains tubular polarity by regulation of cellular transport sodium and potassium in proximal tubules. NaK-ATPase is hnked to the cytoskeleton/ membrane complex by a variety of proteins including spectrin. It has been demonstrated that in early reperfusion period spectrin dissociates from the cytosleleton and NaK-ATPase moves from the basolateral membrane into the cytoplasm and apical membrane [54-58]. 

The major effect is on the distal tubules of nephrons, where aldosterone promotes sodium retention and potassium excretion. Under the influence of aldosterone, sodium ions are actively transported out of the distal tubular cell into blood, and this transport is coupled to passive potassium flux in the opposite direction. Consequently, intracellular [Na" ] is diminished and intracellular [K+] is elevated. This intracellular diminution of [Na+] promotes the diffusion of sodium from the filtrate into the cell, and potassium diffuses into the filtrate. Aldosterone also stimulates sodium reabsorption from salivary fluid in the salivary gland and from luminal fluid in the intestines, but these sodium-conserving actions are of minor importance. 

Within the proximal tubules, the bulk of filtered solutes (e.g., glucose, amino acids, bicarbonate, potassium) and a large proportion of filtered sodium are reabsorbed with water. The luminal portion of the tubular cells is equipped with numerous transport... 

B. Effects In full doses, thiazides produce moderate but sustained sodium and chloride diuresis. Hypokalemic metabolic alkalosis may occur (Table 15-2). Reduction in the transport of sodium into the tubular cell reduces intracellular sodium and promotes sodium-calcium exchange. As a result, reabsorption of calcium from the urine is increased and urine calcium content is decreased— the opposite of the effect of loop diuretics. Because they act in a diluting segment of the nephron, thiazides may interfere with excretion of water and cause dHutional hyponatremia. 

Aldosterone maintains the sodium levels of the body by stimulating the reabsorption of sodium in the renal tubules. In adrenalectomized dogs and in patients with Addison s disease, sodium excretion is proportional, but not equal, to glomerular filtration. Aldosterone acts in the distal tubule at the site of sodium reabsorption and potassium excretion, but much of the information on aldosterone s mode of action and on renal tubular cells has been obtained indirectly by studying the effect of the hormone on simpler systems. Aldosterone stimulates active sodium transport across the bladder and skin of toads. This effect of aldosterone is manifest only after a lag period. 

An essential requirement for diffusion of Na+ ions is the creation of a concentration gradient for sodium between the filtrate and intracellular fluid of the epithelial cells. This is accomplished by the active transport ofNa+ ions through the basolateral membrane of the epithelial cells (see Figure 19.4). Sodium is moved across this basolateral membrane and into the interstitial fluid surrounding the tubule by the Na+, K+-ATPase pump. As a result, the concentration of Na+ ions within the epithelial cells is reduced, facilitating the diffusion of Na+ ions into the cells across the luminal membrane. Potassium ions transported into the epithelial cells as a result of this pump diffuse back into the interstitial fluid (proximal tubule and Loop of Henle) or into the tubular lumen for excretion in the urine (distal tubule and collecting duct). 

Because the transport of sodium is an active process, it is used to accumulate NaCl in the interstitial fluid of the medulla. In fact, this activity is involved in the initial establishment of the vertical osmotic gradient. Furthermore, sodium is actively transported out of the tubular epithelial cells up its concentration gradient until the filtrate is 200 mOsm/1 less concentrated than the surrounding interstitial fluid. This difference between the filtrate and the interstitial fluid is referred to as the horizontal osmotic gradient. Because the filtrate at the end of the Loop of Henle has an osmolarity of 100 mOsm/1, the kidneys have the ability to produce urine that is significantly more dilute than the plasma. 

Mineralocorticoids are believed to increase sodium reabsorption by affecting sodium channels and sodium pumps on the epithelial cells lining the renal tubules.18,58 Mineralocorticoids ability to increase the expression of sodium channels is illustrated in Figure 29-5. These hormones enter the tubular epithelial cell, bind to receptors in the cell, and create an activated hormone-receptor complex.18 This complex then travels to the nucleus to initiate transcription of messenger RNA units, which are translated into specific membrane-related proteins.27,58 These proteins in some way either create or help open sodium pores on the cell membrane, thus allowing sodium to leave the tubule and enter the epithelial cell by passive diffusion.27,83 Sodium is then actively transported out of the cell and reabsorbed into the bloodstream. Water reabsorption is increased as water follows the sodium movement back into the bloodstream. As sodium is reabsorbed, potassium is secreted by a sodium-potassium exchange, thus increasing potassium excretion (see Fig. 29-5). 

Sodium bicarbonate reabsorption by the proximal tubule is initiated by the action of a Na+/H+ exchanger located in the luminal membrane of the proximal tubule epithelial cell (Figure 15-3). This transport system allows sodium to enter the cell from the tubular lumen in exchange for a proton from inside the cell. As in all portions of the nephron, Na+/K+ ATPase in the basolateral... 

As the filtrate flows into the descending limb of this loop, the NaCl concentration in the fluid surrounding the tubule increases by a factor of four, and osmotic processes cause water to be reabsorbed. At the same time, salts and metabolic products are secreted into the tubular fluid. In the ascending limb, in contrast, the tubular wall is nearly impermeable to water. Here, the epithelial cells contain molecular pumps that transport sodium and chloride from the tubular fluid into the space between the nephrons (the interstitium). These processes are accounted for in considerable detail in the spatially extended model developed by Holstein-Rathlou et al. [14]. In the present model, the reabsorption l rmh in the proximal tubule and the flow resistance Rum are treated as constants. Without affecting the composition much, the proximal tubule reabsorbs close to 60% of the ultrafiltrate produced by the glomerulus. 

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